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Nat Commun ; 5: 4825, 2014 Sep 08.
Article in English | MEDLINE | ID: mdl-25198699

ABSTRACT

Human pluripotent stem cells (hPSCs) tend to acquire genomic aberrations in culture, the most common of which is trisomy of chromosome 12. Here we dissect the cellular and molecular implications of this trisomy in hPSCs. Global gene expression analyses reveal that trisomy 12 profoundly affects the gene expression profile of hPSCs, inducing a transcriptional programme similar to that of germ cell tumours. Comparison of proliferation, differentiation and apoptosis between diploid and aneuploid hPSCs shows that trisomy 12 significantly increases the proliferation rate of hPSCs, mainly as a consequence of increased replication. Furthermore, trisomy 12 increases the tumorigenicity of hPSCs in vivo, inducing transcriptionally distinct teratomas from which pluripotent cells can be recovered. Last, a chemical screen of 89 anticancer drugs discovers that trisomy 12 raises the sensitivity of hPSCs to several replication inhibitors. Together, these findings demonstrate the extensive effect of trisomy 12 and highlight its perils for successful hPSC applications.


Subject(s)
Carcinogenesis/genetics , Cell Proliferation/genetics , Chromosomes, Human, Pair 12/genetics , Gene Expression Regulation, Neoplastic/genetics , Neoplasms/genetics , Pluripotent Stem Cells/metabolism , RNA, Messenger/metabolism , Trisomy/genetics , Aneuploidy , Cell Culture Techniques , Cell Line, Tumor , Embryonal Carcinoma Stem Cells/metabolism , Gene Expression/genetics , Gene Expression Profiling , Humans , In Vitro Techniques , Neoplasms, Germ Cell and Embryonal/genetics , Teratocarcinoma/genetics , Teratoma/genetics
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